The purposes of the research supported under this contract are to determine the toxicity of two members of the tricothecene mycotoxins, (anguidine, (das) and nivalenol) including their gross and microscopic effects; absorption, distribution and excretion by several routes of administration; to identify and synthesize the more prominent metabolites, and to identify or synthesize compounds which will block or reduce the toxicity of DAS and nivalenol. During the past year we developed a method for tropical exposure to the mycotoxins in rodents which confirms our observations by other routes of administration that there is a significant difference in sensitivity between rats and mice. The mouse excretes 80% of a dose of DAS within 24 hours, 90% of which appear in the urine. This is in contrast to most literature reports on other tricothecenes (T-2) where the feces is the major route of excretion. A detailed analysis of distribution and excretion by topical application is in progress. We have developed a system (colony forming unit) to study stem cells of the bone marrow of rodents exposed to DAS. Long-term effects of DAS on hematology and on immunocompetence are in progress using this system and acute stem-cell effects are under study. In the rodent the testes is the first and most sensitive organ as an indicator of DAS toxicity and is being used to detect earliest effects and correlate these with metabolites in animals exposed by different routes of exposure.

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